Biomedical subjects

M Rowland

Publications and source records attributed to M Rowland.

At least 55 records · Page 3Linked to original sources

PubMed1999

Development of an assay for the extraction and quantification of nine 5-n-alkyl-5-ethyl barbituric acids in various rat tissues.

Methods were developed to quantify a series of nine homologous 5-n-alkyl-5-ethyl barbituric acids in 15 rat tissues. Tissue homogenates were spiked with one of four multicomponent mixtures (methyl to n-propyl, n-propyl to n-pentyl, n-pentyl to n-heptyl and n-pentyl to n-nonyl). Liquid-liquid extraction was used to extract the homologues from the rat tissues. Reverse phase HPLC with UV detection at 214 nm was used to separate and quantify the individual barbiturates. The limit of detection for each respective homologue was 1 microg x g(-1) except skin and bone (2 microg x g(-1)). The methodology developed reduced a potential 135 individual assays to a more manageable 16.

Animals↗

PubMed1999

Physiologically based pharmacokinetics of cyclosporine A: reevaluation of dose-nonlinear kinetics in rats.

The disposition kinetics of Cyclosporine A (CyA) in rat, based on measurement in arterial blood, appeared dose-linear over a wide i.v. dose range (1.2-30 mg/kg). Physiologically based pharmacokinetic (PBPK) analysis, however, demonstrated that this was an apparent observation resulting from counterbalancing nonlinear factors, such as saturable blood and tissue distribution, as well as clearance (CLb). A PBPK model was successfully developed taking into account these multiple nonlinear factors. Tissue distribution was distinctly different among various organs, being best described by either a linear model (muscle, fat; Model 1), one involving instantaneous saturation (lung, heart, bone, skin, thymus; Model 2), noninstantaneous saturation (kidney, spleen, liver, gut; Model 3), or one with saturable efflux (brain; Model 4). Overall, the whole body volume of distribution at steady state for unbound CyA (Vuss) decreased with increasing dose, due at least in part to saturation of tissue-cellular cyclophilin binding. Clearance, essentially hepatic, and described by the well-stirred model, was also adequately characterized by Michaelis-Menten kinetics, Km 0.60 microgram/ml. In model-based simulations, both volume of distribution at steady state (Vss,b) and CLb varied in a similar manner with dose, such that terminal t1/2 remained apparently unchanged; these dose responses were attenuated by saturable blood binding. CyA concentration measured in arterial blood was not always directly proportional to the true exposure, i.e., unbound or target tissue concentrations. The PBPK model not only described comprehensively such complicated PK relationships but also permitted assessment of the sensitivity of individual parameters to variation in local nonlinear kinetics. Using this approach, dose-dependent CyA uptake into brain was shown to be sensitive to both active and passive transport processes, and not merely the affinity of the active (efflux) transporter at the level of the blood-brain barrier.

Animals↗

PubMed1999

Control of zoophilic malaria vectors by applying pyrethroid insecticides to cattle.

The principal method of malaria control in South and West Asia--indoor residual spraying--is extravagant with insecticide. A more efficient way of deploying insecticide might be to apply it on livestock since the malaria vectors in the region are highly zoophilic. A series of investigations assessed the potential of cattle treated with pyrethroid to control zoophilic mosquitoes. Permethrin, deltamethrin, and lambdacyhalothrin were applied to cattle using a sponge at concentrations of 0.5 g/m2, 0.025 g/m2, and 0.025 g/m2, respectively. 'Whole animal' insecticide bioassays that simulated natural mosquito-host contact were used to measure insecticidal and behavioural effects on wild host-seeking mosquitoes. The bioassays were performed on both sheltered and outdoor grazing animals for up to 45 days post-treatment. The possibility that treatments might cause diversion of host-seeking vectors from cattle to people nearby was also investigated. At the doses tested deltamethrin had the most pronounced and longest-lasting effect, reducing the proportion of bloodfed survivors by over 50% for the first two weeks. The majority of mosquitoes affected by the insecticide were killed before feeding. Insecticidal impact was generally lower on grazing than on sheltered animals. There was no diversion of host-seeking mosquitoes from treated cattle to nearby humans at any stage after treatment. The application of insecticide to livestock using a campaign approach may prove an effective means of controlling malaria in the region. At the doses tested deltamethrin is the most appropriate insecticide for this purpose.

Administration, Topical↗

PubMed1999

Low rates of Helicobacter pylori reinfection in children.

BACKGROUND & AIMS: Reinfection after treatment for Helicobacter pylori is uncommon in adults. It is more likely to occur in children because they acquire primary infection. The aim of this study was to determine whether children are likely to become reinfected with H. pylori and if there are any risk factors for reinfection. METHODS: A prospective study of children who had documented evidence of successful treatment for H. pylori infection was performed. Sixty children were eligible for inclusion; results for 52 are presented. Children, parents, and siblings underwent [(13)C]urea breath tests. Details of family size and socioeconomic status were documented. Cox logistic regression analysis was used to determine the risk factors for reinfection. RESULTS: The duration of follow-up was 103.8 patient-years (mean +/- SD, 24 +/-14.0 months). Forty-six (88.5%) of the index children remained clear of infection, and 6 (11.5%) children were reinfected. The mean age of those who became reinfected was 5.8 +/- 5.6 years compared with 12.3 +/- 3.0 years for those who remained clear of infection (P = 0.00001). Only 2 of 46 (4.3%) children older than 5 years of age were reinfected, although 80.8% had 1 infected parent and 65% of siblings were infected. Reinfection rate was 2.0% per person per year in children older than 5 years. Living with infected parents and siblings and low socioeconomic status were not risk factors for reinfection. In logistic regression analysis, age was the only risk factor for reinfection. CONCLUSIONS: Reinfection with H. pylori occurs rarely in children older than 5 years of age regardless of socioeconomic group or number of infected family members. These findings also indicate that it is not necessary to treat all family members to achieve long-term eradication of H. pylori.

Adolescent↗

PubMed1999

How should Helicobacter pylori infected children be managed?

It is now recognised that Helicobacter pylori, like most enteric infections, is mainly acquired in childhood. Adults rarely become infected, with seroconversion rates varying between 0.33and 0.5% per person year. The age at which children are most likely to become infected is still unclear, but findings in a number of cross-sectional studies suggest that infection is acquired before the age of five. The prevalence of infection is highest in children in the developing world where up to 75% of children may be infected by the age of 10. In the developed world the prevalence of infection is noticeably increased among socially deprived children. The diagnosis of H pylori infection in childhood is most often made at endoscopy, for which there are many indications. Symptoms such as abdominal pain, vomiting, and haematemesis may be associated with duodenal ulcer and H pylori infection. However, in the case of children undergoing endoscopy for assessment of oesophagitis, failure to thrive, coeliac disease, Crohn's disease, or portal hypertension, the finding of H pylori infection is likely to be incidental. How should we manage these children with a diagnosis of H pylori infection? Currently, there are no consensus guidelines for the management of H pylori infected children. In 1994 the National Institutes of Health consensus statement recommended that adults with gastric or duodenal ulcer disease, who are infected with H pylori, should receive antimicrobial treatment. The European Maastricht Consensus Report suggested broader indications for treatment of infected adults. It states that treatment is advisable for all H pylori infected dyspeptic patients diagnosed non-invasively under 45 years of age at a primary care level. Patients older than 45 years with dyspeptic symptoms should be treated for H pylori infection but only after endoscopy to rule out any other underlying pathology. The European guidelines also recommend treatment for infected patients with mucosa associated lymphoid tissue lymphoma and patients who are found to have intestinal metaplasia and gastric atrophy.

Anti-Bacterial Agents↗

PubMed1999

Empirical versus mechanistic modelling: comparison of an artificial neural network to a mechanistically based model for quantitative structure pharmacokinetic relationships of a homologous series of barbiturates.

The aim of the current study was to compare the predictive performance of a mechanistically based model and an empirical artificial neural network (ANN) model to describe the relationship between the tissue-to-unbound plasma concentration ratios (Kpu's) of 14 rat tissues and the lipophilicity (LogP) of a series of nine 5-n-alkyl-5-ethyl barbituric acids. The mechanistic model comprised the water content, binding capacity, number of the binding sites, and binding association constant of each tissue. A backpropagation ANN with 2 hidden layers (33 neurons in the first layer, 9 neurons in the second) was used for the comparison. The network was trained by an algorithm with adaptive momentum and learning rate, programmed using the ANN Toolbox of MATLAB. The predictive performance of both models was evaluated using a leave-one-out procedure and computation of both the mean prediction error (ME, showing the prediction bias) and the mean squared prediction error (MSE, showing the prediction accuracy). The ME of the mechanistic model was 18% (range, 20 to 57%), indicating a tendency for overprediction; the MSE is 32% (range, 6 to 104%). The ANN had almost no bias: the ME was 2% (range, 36 to 64%) and had greater precision than the mechanistic model, MSE 18% (range, 4 to 70%). Generally, neither model appeared to be a significantly better predictor of the Kpu's in the rat.

Algorithms↗

PubMed1999

Distribution kinetics of salicylic acid in the dual-perfused rat liver preparation.

The hepatic distribution kinetics of salicylic acid was determined using a single-pass dual hepatic artery (HA) and portal vein (PV) perfused in situ rat liver preparation. Bolus doses of [14C]salicylic acid and of reference markers ([3H]-water and [14C]-sucrose) were injected in a random order into either the HA or PV and then, after an appropriate interval, into the alternate vessel. The hepatic outflow profile of [14C]salicylic acid displayed a characteristic sharp peak followed by a slower eluting tail, whereas sucrose and water displayed unimodal outflow profiles. The biphasic outflow profile indicates that the hepatic distribution of salicylic acid is not instantaneous but is limited by a permeability barrier. The in situ permeability surface area product for [14C]salicylic acid was 3.35 +/- 0.26 ml/min/g for PV and 7.45 +/- 1. 50 ml/min/g for HA administration. Furthermore, theory dictates that hepatic uptake is influenced by both perfusion and permeability if effective permeability surface area product/blood flow ratio lies between the values of 0.06 and 7.0. Our estimates (3.0 for venous output and 6.7 for arterial input) indicate that hepatic uptake of salicylic acid is dependent on both perfusion and permeability. The volume terms were calculated using two different methods, standard and specific. Regardless of the compound and method, the volume of distribution after arterial administration was larger than that after venous administration. In addition, a volume of distribution approximately twice that of the total aqueous space (i.e., HA, 2.23 +/- 0.13 versus 1.10 +/- 0.07 ml/g; PV, 1.72 +/- 0.16 versus 0.68 +/- 0.04 ml/g) implies that salicylic acid has a significant affinity for hepatic tissue. A similar tissue-to-perfusate partition coefficient associated with HA and PV input (5.40 +/- 0.38 versus 6. 48 +/- 0.56) indicates that affinity of salicylic acid for hepatic tissue is independent of the route of input.

Animals↗

PubMed1999

Modulation of the permeability of H2 receptor antagonists cimetidine and ranitidine by P-glycoprotein in rat intestine and the human colonic cell line Caco-2.

The influence of secretory transporters on intestinal permeability characteristics of the H2 receptor antagonists ranitidine and cimetidine was studied in Caco-2 monolayers and rat intestinal mucosa mounted in Ussing chambers. Both drugs exhibited vectorial transport across rat ileum with significantly greater (2-4-fold) permeability in the serosal-to-mucosal than the mucosal-to-serosal direction, indicative of net mucosal secretion. Mucosal ranitidine secretion was also observed in rat distal colon, although to a lesser degree. Ileal ranitidine secretion was concentration dependent and significantly reduced by the P-glycoprotein (P-gp) substrates verapamil and cyclosporin. In contrast, probenicid, an inhibitor of the multidrug-related protein, had no effect on ranitidine permeability. The paracellular marker mannitol showed no evidence of asymmetric permeability or sensitivity to P-gp inhibitors. Significant expression of P-gp protein in rat intestinal epithelial cells was confirmed by immunoblotting. Caco-2 monolayers, which overexpress P-gp, also showed asymmetric permeability of ranitidine and cimetidine. In this model, ranitidine permeability in the mucosal-to-serosal direction decreased by approximately 95% as monolayer resistance increased from 150 to 500 Omega/cm2, indicating a primarily paracellular route of transport. However, serosal-to-mucosal permeability was insensitive to resistance changes, consistent with a primarily transcellular route in this direction. These data indicate that ranitidine and cimetidine can act as substrates for intestinal P-gp and suggest that the balance between absorptive and secretory mechanisms as a factor in determining intestinal absorption needs to be a routine consideration even for compounds expected to have a predominantly paracellular route of absorption.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

In vitro studies of teicoplanin binding to rat tissues and erythrocytes.

Teicoplanin is a large polar antibiotic with a large distribution volume (Vss = 1.2-2.8 l/kg) despite extensive binding to plasma albumin. To understand this observation, binding of 3H-teicoplanin to 10% rat tissue homogenates was determined in vitro by ultracentrifugation in the presence of teicoplanin (1-30 microg/ml). Binding and efflux from erythrocytes were also studied. The in vitro total-to-unbound tissue concentration ratio (Kpu) differed widely but for each tissue was concentration independent. Upon correction for the plasma unbound fraction, there was discrepancy between the in vitro and in vivo tissue-to-plasma concentration ratios (KP), the latter calculated from previously published tissue and plasma concentration-time data using the area method. Moreover, calculation of Vss from in vitro Kp (8.10 l/kg) overestimated the in vivo value. These results suggest that in vivo teicoplanin binds to cell membranes and enters some but not all cells, such as erythrocytes.

Animals↗

PubMed1998

Plasma and tonsillar tissue pharmacokinetics of teicoplanin following intramuscular administration to children.

The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administration. Thirty seven patients in all received either a single 5 mg/kg dose; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 x 5 mg/kg dosing schedule). All plasma data were analyzed simultaneously by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted to the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.020-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54-0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-order transfer model for distribution of teicoplanin between plasma and tonsillar tissue was fitted to the tonsil data. The mean parameter values (95% confidence intervals) were: transfer rate constant between plasma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants correspond to a distribution half-life of 0.95 h and an equilibrium distribution concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight, there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulations were used, one for the 5 mg/kg dose and the other for the 10 mg/kg dose, no effect of formulation on the pharmacokinetics of teicoplanin after im (intramuscular) administration was found.

Algorithms↗

PubMed1998

Development of an optimal method for the dual perfusion of the isolated rat liver.

The liver receives two blood supplies, the portal vein (PV) and hepatic artery (HA). The isolated perfused rat liver preparation (IPRL) is widely used to examine physiological factors affecting the hepatic disposition of compounds, but usually it is perfused via the PV only. In the development of a more physiological dual perfused system, we examined three surgical procedures for HA perfusion--cannulation through the gastroduodenal artery, the aorta, and the celiac artery--using 14C-urea as the reference marker. Similar efflux profiles for 14C-urea were obtained for all three procedures, with a clear difference between HA and PV administration; however, cannulation of blood vessels and isolation of the HA supply were the most reliable with the celiac artery cannulation, making it the preferred procedure.

Animals↗

PubMed1998

Species differences in size discrimination in the paracellular pathway reflected by oral bioavailability of poly(ethylene glycol) and D-peptides.

Animal models are frequently used to aid prediction of intestinal absorption in humans. However, there is little comparative quantitative information on species differences in paracellular permeation, which is an important route for oral absorption of small to medium-sized hydrophilic drug molecules. This study addresses this issue by comparing the molecular mass (MM) dependency in oral bioavailability between rat and dog of poly(ethylene glycol) (PEG), a polydispersed model mixture commonly used to characterize paracellular absorption, and of a series of eight D-peptides (based on D-phenylalanine). Fasted rats and dogs received PEG (400/900) and the D-peptides (MM 236-406 Da), orally and intravenously, with total 24-48 h urine collection to estimate oral bioavailability. After HPLC separation, the individual PEG oligomers and D-peptides were determined using radiometric detection, for radiolabeled material, and LC-MS, for unlabeled (PEG) material. All compounds were predominantly excreted unchanged following intravenous administration. After oral administration, the predominant peak in the radiochromatogram was unchanged material, indicating stability of the compounds in the gastrointestinal tract. A clear molecular mass dependency in oral bioavailability was seen with both series, but with absorption much greater in dog than rat. Thus, for PEG in rat, bioavailability decreased sharply from 79 to around 2% with increasing MM between 282 and 591 Da, and then tapered to around 1. 5% up to 1295 Da. Whereas in dog, bioavailability remained around 100% for oligomers up to 600 Da and then decreased quite sharply with increasing MM, tending to plateau around 13% beyond 900 Da. Likewise, for the d-peptides in rat, bioavailability decreased from 30 to 1% with increasing MM between 236 and 406 Da, whereas in dog it was 100%, declining to 16% over the same molecular range. This species difference appears to be due to a larger pore size and greater frequency of pores in the paracellular pathway of dog compared to rat. Furthermore, on the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human.

Absorption↗

PubMed1998

What surface of the intestinal epithelium is effectively available to permeating drugs?

A mathematical model is presented which examines the extent to which the intestinal epithelium is accessed by drug molecules. Morphological information from the literature for the jejunum, ileum, and colon of the rat and for human jejunum was incorporated. Perturbation theory was used to derive the limiting cases for total access to the entire epithelial surface, for transport by diffusion and by diffusion with convection, respectively. A parameter gamma = square root of (Ph2)/(Db) was identified to provide a measure of the ability of drug molecules to access the entire epithelial surface down to the crypt wells, where P is the cell permeability, D the aqueous diffusion coefficient, h the channel depth between the villi, and b is half the width of the idealized intervillous channel. When gamma << 1, diffusion is not a limitation and the entire surface is fully utilized for absorption of drug. This condition arises with drugs of low permeability and is more likely to be met with colonic than small intestinal epithelium. When gamma >/= 1, diffusion becomes a limitation and then not all of the epithelial surface is functionally accessible to drug molecules, a condition most likely to prevail with drugs of high permeability traversing the jejunum. Furthermore, water flux per se is predicted to have relatively little influence on enhancing surface accessibility. This simple, but quantitative approach showed that the ranking order of permeability jejunum >ileum> colon for low permeable drugs can at least in part be explained by the differences in surface amplification between these different epithelial regions. The analysis also indicates that for highly permeable drugs extreme caution should be exercised in extrapolating permeability measurements in vitro across various preparations and to events in vivo.

Animals↗

PubMed1998

Quantitative structure-pharmacokinetics relationships: II. A mechanistically based model to evaluate the relationship between tissue distribution parameters and compound lipophilicity.

The tissue-to-unbound plasma distribution coefficients (Kpus) of 14 rat tissues after i.v. administration of nine 5-n-alkyl-5-ethyl barbituric acids, determined in a previous study, were used to identify a model of the relationship between tissue distribution and lipophilicity of the homologs, expressed in terms of their octanol to water partition ratio, P. Based on mechanistic considerations and assumptions, the parameter model was expressed as Kpu tau = fw.tau [1 + a tau (nPt.tau)Pb tau], where fw.tau is the tissue water content. (nPt. tau) is the binding capacity of the tissue, n is the number of the binding sites, a tau and b tau are the parameters of the relationship Ka tau = a tau Pb tau; and Ka tau is the binding association constant of each tissue. The parameter model was linearized and fitted to the predetermined Kpu values, yielding correlation coefficients ranging between .940 and .997. The predictive performance of the parameter model was evaluated using a leave-one-out procedure with subsequent computation of the mean prediction error (ME = measurement of the prediction bias) and the square root of the mean squared prediction error (RMSE = measurement of the prediction accuracy). The ME varied between -22.48 and 61.14%, indicating a slight tendency for overpredicting. The RMSE was between 24.73 and 102% for the individual tissues across the different homologs; and between 28.33 and 85.2% for the individual homologs across the different tissues. The apparently high Kpu prediction errors, when translated through the low sensitivity of the barbiturate whole-body physiologically based pharmacokinetic model, established previously, leads to predicted tissue concentration-time profiles within 5 to 20% of the original ones. Therefore, it is concluded, that the identified mechanistically based model is a good predictor of the tissue-to-unbound Kpus in the rat tissues.

Animals↗

PubMed1998

Optimal experimental design for precise estimation of the parameters of the axial dispersion model of hepatic elimination.

The axial dispersion model of hepatic drug elimination is characterized by two dimensionless parameters, the dispersion number, DN, and the efficiency number, RN, corresponding to the relative dispersion of material on transit through the organ and the relative efficiency of elimination of drug by the organ, respectively. Optimal design theory was applied to the estimation of these two parameters based on changes in availability (F) of drug at steady state for the closed boundary condition model, with particular attention to variations in the fraction of drug unbound in the perfusate (fuB). Sensitivity analysis indicates that precision in parameter estimation is greatest when F is low and that correlation between RN and DN is high, which is desirable for parameter estimation, when DN lies between 0.1 and 100. Optimal design points were obtained using D-optimization, taking into account the error variance model. If the error variance model is unknown, it is shown that choosing Poisson error model is reasonable. Furthermore, although not optimal, geometric spacing of fuB values is often reasonable and definitively superior to a uniform spacing strategy. In practice, the range of fuB available for selection may be limited by such practical considerations as assay sensitivity and acceptable concentration range of binding protein. Notwithstanding, optimal design theory provides a rational approach to precise parameter estimation.

Linear Models↗

PubMed1998

Lumping of whole-body physiologically based pharmacokinetic models.

Lumping is a common pragmatic approach aimed at the reduction of whole-body physiologically based pharmacokinetic (PBPK) model dimensionality and complexity. Incorrect lumping is equivalent to model misspecification with all the negative consequences to the subsequent model implementation. Proper lumping should guarantee that no useful information about the kinetics of the underlying processes is lost. To enforce this guarantee, formal standard lumping procedures and techniques need to be defined and implemented. This study examines the lumping process from a system theory point of view, which provides a formal basis for the derivation of principles and standard procedures of lumping. The lumping principle in PBPK modeling is defined as follows: Only tissues with identical model specification, and occupying identical positions in the system structure should be lumped together at each lumping iteration. In order to lump together parallel tissues, they should have similar or close time constants. In order to lump together serial tissues, they should equilibrate very rapidly with one another. The lumping procedure should include the following stages: (i) tissue specification conversion (when tissues with different model specifications are to be lumped together); (ii) classification of the tissues into classes with significantly different kinetics, according to the basic principle of lumping above; (iii) calculation of the parameters of the lumped compartments; (iv) simulation of the lumped system; (v) lumping of the experimental data; and (vi) verification of the lumped model. The use of the lumping principles and procedures to be adopted is illustrated with an example of a commonly implemented whole-body physiologically based pharmacokinetic model structure to characterize the pharmacokinetics of a homologous series of barbiturates in the rat.

Algorithms↗

PubMed1998

Clinical significance of Helicobacter infection in children.

Helicobacter pylori infection of the gastric mucosa causes chronic gastritis and is associated with peptic ulcer disease and gastric carcinoma. These are conditions which usually occur in adult life. However, H. pylori is an infection which is mainly acquired in childhood. The overall prevalence of H. pylori in children is 10% in developed countries but can be as high as 30-40% in children from lower socio-economic groups. In developing countries, the prevalence of H. pylori in children ranges from 80-100%. H. pylori gastritis does not appear to be associated with symptoms in children in the absence of duodenal ulcer disease. H. pylori infection is present in the vast majority of children with duodenal ulcer disease and, as in adults, eradication of the organism results in long-term healing of duodenal ulceration. H. pylori infection acquired in childhood is now considered to be a significant risk factor for the development of gastric carcinoma. The World Health Organization has classified H. pylori as a Group 1 carcinogen. Specific epidemiological questions which need to be answered in children include the age at which infection is acquired, specific risk factors for infection, the mode of transmission and the risk of reinfection following treatment. Recently, a one week treatment regimen using colloidal bismuth subcitrate, metronidazole and clarithromycin has been shown to be effective in treating children, but compliance is important. Currently there are no guidelines on the need to treat children and a consensus is urgently required on this issue.

Adolescent↗

PubMed1998

Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease.

BACKGROUND: Duodenal ulcer disease is strongly associated with Helicobacter pylori infection of the gastric mucosa. Eradication of H pylori from the gastric mucosa in adults is associated with long term healing of ulcers. AIMS: To follow a cohort of children with duodenal ulcer disease for a minimum of two years after the eradication of H pylori. PATIENTS AND METHODS: Over a three year period, all children diagnosed with duodenal ulcer disease had their symptoms documented and their H pylori status evaluated. The histories of these children were carefully screened to determine previous symptoms and to document previous treatment regimens. RESULTS: Sixteen children were diagnosed with ulcers and 15 were available for treatment and long term follow up. The median age at which symptoms first occurred was 10.5 years (range, 6-14) and the median duration of symptoms was 24 months (range, 2-60). Ten of the children had been treated with H2 receptor antagonists for a median of 3.5 months (range, 1-60). Duodenal ulcers healed in all children after eradication of H pylori and all children have remained asymptomatic for a median of 37 months (range, 26-62). No child has required subsequent admission to hospital. CONCLUSION: Eradication of H pylori is very effective in the long term healing of duodenal ulcer disease. H pylori eradication should be the standard treatment for all infected children who present with duodenal ulcer disease.

Adolescent↗